Canertinib or CI-1033 (N-[4-[N-(3-Chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]acrylamide) is a pan-erbB tyrosine kinase inhibitor. It selectively inhibits erbB1 (epidermal growth factor receptor), erbB2, erbB3, and erbB4 without inhibiting tyrosine kinase activity of receptors such as platelet-derived growth factor receptor, fibroblast growth factor receptor, and insulin receptor, even at high concentrations. Canertinib was under development by Pfizer Inc as a potential treatment for cancer.

Varlitinib (Alternative Names: ARRY-334543; ARRY-543; ASLAN-001; Varlitinib tosylate) is a small molecule based reversible pan-HER inhibitor of EGFR, HER2 and HER4. In response to the binding of various ligands, these kinases undergo heterodimerisation and homodimerization, resulting in activation of numerous growth factor signaling pathways, by inhibiting the activation of the HER receptors via drug, effects such as shrinkage of the tumor and longer survival can be anticipated. In a large variety of cancers, the overexpression and/or constitutive activation of EGFR and HER2 are often observed and frequently correlate with poor clinical prognosis. Licensed from Array BioPharma with global rights for all indications, varlitinib is being developed as first-in-class drug for cholangiocarcinoma, gastric and colorectal cancer, and as best-in-class drug for breast cancer.

Tesevatinib (EXEL-7647 or XL647) was optimized as an inhibitor of a spectrum of growth-promoting and angiogenic receptor tyrosine kinases (RTKs) to simultaneously block tumor growth and vascularization. In particular, Tesevatinib potently inhibits the EGF/ErbB2, VEGF, and ephrin RTK families. The drug is being developed by Kadmon Corporation under licence from Symphony Evolution (Symphony Capital Partners). Kadmon is developing tesevatinib for the treatment of autosomal polycystic kidney disease and solid cancers.

AG1478 (also known as Tyrphostin AG 1478 ) is a selective EGFR inhibitor, which induced cell cycle arrest in G1 phase, is developed as potential drug for nasopharyngeal carcinoma treatment. In addition was shown, that AG1478 effectively blocked the leiomyoma cell growth and is unaffected by the presence of physiological concentrations of progesterone and estradiol. The growth-arresting properties of AG1478, unaffected by ovarian steroidal hormones, identify it as a potential lead agent for the non-surgical management of uterine leiomyomas. Also was investigated the action of the combination AG1478 in combination with HGF tyrosine kinase inhibitors on non-small cell lung cancer (NSCLC) cells, and was suggested, that these combinations of drugs could be potentially used for treatment of NSCLC.

Mobocertinib (EXKIVITY™) is a first-in-class EGFR tyrosine kinase inhibitor being developed for the treatment of EGFR exon 20 insertion (EGFRex20ins) -positive non-small cell lung cancer (NSCLC). Mobocertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild type (WT) EGFR. Two pharmacologically-active metabolites (AP32960 and AP32914) with similar inhibitory profiles to mobocertinib have been identified in the plasma after oral administration of mobocertinib. In vitro, mobocertinib also inhibited the activity of other EGFR family members (HER2 and HER4) and one additional kinase (BLK) at clinically relevant concentrations (IC50 values <2 nM). Based on efficacy in patients whose disease had progressed on or after platinum-based therapy in a phase I/II trial, mobocertinib was recently granted accelerated approval in the USA in this indication. The drug is also being assessed for marketing approval in various other countries and territories including the EU and China.

Adenosine triphosphate (ATP) is an adenine nucleotide containing three phosphate groups esterified to the sugar moiety. Adenosine triphosphate is the energy source in living cells. In physiological conditions, the average concentration varies from 3150 mM in mammalian cells to 1500–1900 mM in human blood cells. Extracellular adenosine and adenosine triphosphate (ATP) are involved in biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation, signal transduction and secretion in a variety of cell types. A large family of membrane-bound receptors mediates cell signalling by ATP and adenosine. These purinergic receptors ultimately determine the variety of effects induced by extracellular ATP and adenosine. ATP and adenosine have strong negative chronotropic and dromotropic effects on the mammalian heart. The sensitivity of the sinus node and the atrioventricular node to ATP and adenosine manifests pronounced variability among species. For more than three decades, ATP has been used routinely in Europe in the acute therapy of paroxysmal supraventricular tachycardia. ATPace™, an injectable formulation of adenosine 5′-triphosphate (ATP), was developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardio-cardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. However later ATPace development for the treatment of bradycardia and paroxysmal supraventricular tachycardia was discontinued.

Adenosine triphosphate (ATP) is an adenine nucleotide containing three phosphate groups esterified to the sugar moiety. Adenosine triphosphate is the energy source in living cells. In physiological conditions, the average concentration varies from 3150 mM in mammalian cells to 1500–1900 mM in human blood cells. Extracellular adenosine and adenosine triphosphate (ATP) are involved in biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation, signal transduction and secretion in a variety of cell types. A large family of membrane-bound receptors mediates cell signalling by ATP and adenosine. These purinergic receptors ultimately determine the variety of effects induced by extracellular ATP and adenosine. ATP and adenosine have strong negative chronotropic and dromotropic effects on the mammalian heart. The sensitivity of the sinus node and the atrioventricular node to ATP and adenosine manifests pronounced variability among species. For more than three decades, ATP has been used routinely in Europe in the acute therapy of paroxysmal supraventricular tachycardia. ATPace™, an injectable formulation of adenosine 5′-triphosphate (ATP), was developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardio-cardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. However later ATPace development for the treatment of bradycardia and paroxysmal supraventricular tachycardia was discontinued.

Adenosine triphosphate (ATP) is an adenine nucleotide containing three phosphate groups esterified to the sugar moiety. Adenosine triphosphate is the energy source in living cells. In physiological conditions, the average concentration varies from 3150 mM in mammalian cells to 1500–1900 mM in human blood cells. Extracellular adenosine and adenosine triphosphate (ATP) are involved in biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation, signal transduction and secretion in a variety of cell types. A large family of membrane-bound receptors mediates cell signalling by ATP and adenosine. These purinergic receptors ultimately determine the variety of effects induced by extracellular ATP and adenosine. ATP and adenosine have strong negative chronotropic and dromotropic effects on the mammalian heart. The sensitivity of the sinus node and the atrioventricular node to ATP and adenosine manifests pronounced variability among species. For more than three decades, ATP has been used routinely in Europe in the acute therapy of paroxysmal supraventricular tachycardia. ATPace™, an injectable formulation of adenosine 5′-triphosphate (ATP), was developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardio-cardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. However later ATPace development for the treatment of bradycardia and paroxysmal supraventricular tachycardia was discontinued.

Adenosine triphosphate (ATP) is an adenine nucleotide containing three phosphate groups esterified to the sugar moiety. Adenosine triphosphate is the energy source in living cells. In physiological conditions, the average concentration varies from 3150 mM in mammalian cells to 1500–1900 mM in human blood cells. Extracellular adenosine and adenosine triphosphate (ATP) are involved in biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation, signal transduction and secretion in a variety of cell types. A large family of membrane-bound receptors mediates cell signalling by ATP and adenosine. These purinergic receptors ultimately determine the variety of effects induced by extracellular ATP and adenosine. ATP and adenosine have strong negative chronotropic and dromotropic effects on the mammalian heart. The sensitivity of the sinus node and the atrioventricular node to ATP and adenosine manifests pronounced variability among species. For more than three decades, ATP has been used routinely in Europe in the acute therapy of paroxysmal supraventricular tachycardia. ATPace™, an injectable formulation of adenosine 5′-triphosphate (ATP), was developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardio-cardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. However later ATPace development for the treatment of bradycardia and paroxysmal supraventricular tachycardia was discontinued.